JP2012502979A5 - - Google Patents

Description

A first aspect of the invention is a pyrazolopyridine derivative of formula (I) wherein G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are as defined below, and pharmaceutically acceptable thereof Salts and pharmaceutically active derivatives are provided.
A second aspect of the invention is a pyrazolopyridine derivative of formula (I) wherein G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are as defined below, and pharmaceutically acceptable It relates to the use of salts and pharmaceutically active derivatives as medicaments.
A third aspect of the present invention provides a pharmaceutical composition containing at least one pyrazolopyridine derivative of the present invention, and pharmaceutically acceptable salts and pharmaceutically active derivatives thereof, and pharmaceutically acceptable Relates to carriers, diluents or excipients.
The fourth aspect of the invention affects cardiovascular disorders, respiratory disorders, metabolic disorders, skin disorders, bone disorders, neuroinflammatory and / or neurodegenerative disorders, renal diseases, reproductive disorders, eyes and / or lenses Diseases and / or conditions affecting the inner ear, inflammatory disorders, liver diseases, pain, cancer, allergic disorders, traumatic systemic disorders, septic, hemorrhagic and anaphylactic shock, gastrointestinal diseases or disorders, blood vessels In the preparation of a pharmaceutical composition for the treatment or prevention of a disease or condition selected from angiogenesis and angiogenesis dependence and / or other diseases and disorders associated with nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), Use of the pyrazolopyridine derivatives of the present invention, as well as pharmaceutically acceptable salts and pharmaceutically active derivatives thereof.
The fifth aspect of the present invention affects cardiovascular disorders, respiratory disorders, metabolic disorders, skin disorders, bone disorders, neuroinflammatory and / or neurodegenerative disorders, renal diseases, reproductive disorders, eyes and / or lenses Diseases and / or conditions affecting the inner ear, inflammatory disorders, liver diseases, pain, cancer, allergic disorders, traumatic systemic disorders, septic, hemorrhagic and anaphylactic shock, gastrointestinal diseases or disorders, angiogenesis And angiogenesis dependence, and methods of treating patients suffering from a disease or condition selected from other diseases and / or disorders associated with nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase). This method comprises a pyrazolopyridine derivative of formula (I) wherein G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are as defined below, and pharmaceutically acceptable salts and pharmaceuticals thereof Active derivatives are administered to patients in need thereof.
The sixth aspect of the present invention affects cardiovascular disorders, respiratory disorders, metabolic disorders, skin disorders, bone disorders, neuroinflammatory and / or neurodegenerative disorders, renal diseases, reproductive disorders, eyes and / or lenses Diseases and / or conditions affecting the inner ear, inflammatory disorders, liver diseases, pain, cancer, allergic disorders, traumatic systemic disorders, septic, hemorrhagic and anaphylactic shock, gastrointestinal diseases or disorders, angiogenesis G ₁ , G ₂ , G ₃ , for the treatment of diseases or conditions selected from angiogenesis dependence and other diseases and / or disorders related to nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), G ₄ and pyrazolo pyridine derivative G ₅ are as defined below formula (I), and salts and pharmaceutically their pharmaceutically acceptable About sex derivatives.
A seventh aspect of the invention relates to an intermediate of formula (VIII), wherein G ₂ , G ₃ , G ₄ , G ₅ and R ⁸ are as defined below.
An eighth aspect of the invention relates to an intermediate of formula (X), wherein G ₂ , G ₃ , G ₅ and R ⁸ are as defined below.
A ninth aspect of the invention relates to an intermediate of formula (XII), wherein G ₂ , G ₅ and R ⁸ are as defined below.
A tenth aspect of the present invention relates to an intermediate of formula (XIII), wherein G ₂ , G ₄ , G ₅ and R ⁸ are as defined below.
The eleventh aspect of the present invention relates to a process for the preparation of intermediate compounds of formula (VIII), (X), (XII) or (XIII) of the present invention.
A twelfth aspect of the present invention relates to a process for the preparation of the compounds of formula (I) of the present invention.

Also included are salts formed from acid addition salts formed with inorganic acids (eg, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, etc.), and acetic acid, oxalic acid, tartaric acid, succinic acid. , A salt formed by organic acids such as malic acid, fumaric acid, maleic acid, ascorbic acid, benzoic acid, tannic acid, pamoic acid, alginic acid, polyglutamic acid, naphthalenesulfonic acid, naphthalene disulfonic acid and polygalacturonic acid .
“Pharmaceutically active derivative” means any compound that can provide, directly or indirectly, the activity disclosed herein when administered to an individual. The term “indirect” also encompasses prodrugs that can be converted to the active form of the drug by endogenous enzymes or metabolism. Prodrugs are compounds according to the invention having groups that can be chemically or metabolically degraded, derivatives of compounds exhibiting NADPH oxidase inhibitory activity, and pharmacologically in vivo by solvolysis under physiological conditions. A compound that can be converted to an active compound. The present invention further includes any tautomeric forms of the compounds of the present invention.
The term “cardiovascular disorder or disease” refers to atherosclerosis, in particular hypertension, cardiovascular complications of type I or type II diabetes, intimal thickening, coronary heart disease, cerebrovascular, cardiovascular or arterial. Convulsions, endothelial dysfunction, heart failure including congestive heart failure, peripheral arterial disease, restenosis, stent, stroke, trauma caused by ischemic stroke, vascular complications after organ transplantation, myocardial infarction, hypertension, Atherosclerotic lesion formation, platelet aggregation, angina, aneurysm, aortic dissection, ischemic heart disease, cardiac hypertrophy, pulmonary embolism, thrombosis including deep vein thrombosis, organ transplantation, heart under direct vision Includes angioplasty of ischemic organs including surgery, injury caused by restoration of blood flow or oxygen delivery after ischemia during angioplasty, hemorrhagic shock, heart, brain, liver, kidney, retina and intestine Limited to these Diseases or disorders associated with endothelial dysfunction that is not performed.
The term “breathing disorder or disease” includes bronchial asthma, bronchitis, allergic rhinitis, adult respiratory syndrome, cystic fibrosis, pulmonary viral infection (influenza), pulmonary hypertension, idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease (COPD).
The term “allergic disease” includes hay fever and asthma.
The term “traumatic systemic disorder” includes multiple trauma.
The term “disease or disorder affecting metabolism” includes obesity, metabolic syndrome and type II diabetes.
The term “skin disease or disorder” includes psoriasis, eczema, dermatitis, wound healing and scar formation.
The term “bone disorders” includes osteoporosis, osteoporasis, osteosclerosis, periodontitis and hyperparathyroidism.
The term “neurodegenerative disease or disorder” refers specifically to degeneration or modulation of the central nervous system (CNS) at the level of neurons such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, epilepsy and muscular dystrophy. Includes the disease or condition being characterized. In addition, the term “demyelinating”, including neuroinflammatory and demyelinating conditions or diseases such as leukoencephalopathy and white matter atrophy, means a CNS condition or disease involving the breakdown of myelin around axons. In the context of the present invention, the term demyelinating disease refers to multiple sclerosis, progressive multifocal leukoencephalopathy (PML), myelopathy, any neuroinflammatory condition with autoreactive leukocytes within the CNS, congenital Cells such as metabolic disorders, neuropathy due to abnormal myelination, drug-induced demyelination, radiation-induced demyelination, hereditary demyelination, prion-induced demyelination, encephalitis-induced demyelination or spinal cord injury It is intended to include conditions involving the process of demyelination. Preferably the condition is multiple sclerosis.
The term “renal disease or disorder” includes diabetic nephropathy, renal failure, glomerulonephritis, nephrotoxicity of aminoglycosides and platinum compounds, and overactive bladder. In certain embodiments, the term of the present invention includes chronic kidney disease or disorder.
The term “reproductive disorder or disease” includes erectile dysfunction, fertility disorder, benign prostatic hyperplasia and benign prostatic hypertrophy.
The term “disease or disorder affecting the eye and / or lens” includes cataracts, including diabetic cataract, re-opaqueness of the lens after cataract surgery, diabetic or other forms of retinopathy.
The term “condition affecting the inner ear” includes senile deafness, tinnitus, Meniere's disease and other balance problems, ovarian calculus, vestibular migraine, and noise-induced and drug-induced hearing loss (ototoxicity). ) Is included.
The term “inflammatory disorder or disease” refers to inflammatory bowel disease, sepsis, septic shock, adult respiratory distress syndrome, pancreatitis, traumatic shock, bronchial asthma, allergic rhinitis, rheumatoid arthritis, chronic rheumatoid arthritis Arteriosclerosis, intracerebral hemorrhage, cerebral infarction, heart failure, myocardial infarction, psoriasis, cystic fibrosis, stroke, acute bronchitis, chronic bronchitis, acute bronchitis, chronic bronchiolitis, osteoarthritis, gout, spinal cord Inflammation, ankylosing spondylitis, Reuters syndrome, psoriatic arthritis, spondyloarthritis, juvenile arthritis or juvenile ankylosing spondylitis, reactive arthritis, infectious arthritis or post-infection arthritis, gonococcal joint, syphilitic arthritis, Lyme disease , Arthritis induced by "vasculitis syndrome", polyarteritis nodosa, anaphylactic vasculitis, Luegenec granulomatosis, polymyalgia rheumatica, rheumatoid arthritis H, calcium crystal deposition arthritis, pseudogout, non-arthritic rheumatism, bursitis, tendon synovitis, epicondylar inflammation (tennis elbow), carpal tunnel syndrome, impairment due to repeated use (typing), mixed arthritis, nerve Induced by impaired arthropathy, hemorrhagic arthritis, vascular purpura, hypertrophic osteoarthropathy, multicentric reticulohistiocytosis, certain diseases, blood pigmentation, sickle cell disease and other hemoglobin abnormalities Arthritis, hyperlipoproteinemia, dysgammaglobulinemia, hyperparathyroidism, acromegaly, familial Mediterranean fever, Behcet's disease, systemic autoimmune disease, lupus erythematosus, multiple sclerosis and clones Use of a therapeutically effective amount of a compound represented by disease or diseases such as relapsing polychondritis, chronic inflammatory bowel disease (IBD) or formula (I) sufficient to inhibit NADPH oxidase It refers to a related disease that requires administration to a mammal in an amount.
The term liver disease or disorder includes liver fibrosis, alcohol-induced fibrosis, steatosis and nonalcoholic steatohepatitis.
The term `` arthritis '' means acute rheumatoid arthritis, rheumatoid arthritis, chlamydia arthritis, chronic absorptive arthritis, chyle arthritis, arthritis based on bowel disease, filariatic arthritis, gonococcal arthritis, gouty arthritis, hemophilia arthritis, A therapeutically effective amount of a compound represented by hypertrophic arthritis, juvenile chronic arthritis, Lyme arthritis, neonatal foal arthritis, nodular arthritis, alkaton urinary arthritis, psoriatic arthritis or purulent arthritis, or formula (I) , Meaning a related disease that requires administration to a mammal at a dose sufficient to inhibit NADPH oxidase.
The term “pain” includes hyperalgesia associated with inflammatory pain.
The term “cancer” refers to a carcinoma (eg, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, hemangiosarcoma, endothelial sarcoma, lymphangiosarcoma, lymphatic endothelial tumor, periosteum, mesothelioma Tumor, Ewing tumor, leiomyosarcoma, rhabdomyosarcoma, colon cancer, pancreatic cancer, breast cancer, ovarian cancer, renal cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous carcinoma, papillary carcinoma , Papillary adenocarcinoma, cystadenocarcinoma, medullary cancer, bronchogenic cancer, renal cell carcinoma, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, choriocarcinoma, seminoma, fetal cancer, Wilms tumor, cervical cancer, Testis tumor, lung cancer, small cell lung cancer, lung adenocarcinoma, bladder cancer or epithelial cancer) or a therapeutically effective amount of a compound represented by formula (I) at a dose sufficient to inhibit NADPH oxidase to a mammal It refers to the associated disease that needs to be administered.
The term “gastrointestinal disease or disorder” includes gastric mucosal disorder, ischemic bowel disease management, enteritis / colitis, cancer chemotherapy or neutropenia.
The term “angiogenesis” includes sprouting angiogenesis, stacked angiogenesis, angiogenesis, arteriogenesis and lymphangiogenesis. Angiogenesis is the formation of new blood vessels from existing capillaries or postcapillary venules and occurs in pathological conditions such as cancer, arthritis and inflammation. Organs composed of a wide variety of tissues or organized tissues, including skin, muscle, gastrointestinal tract, connective tissue, joints, bones, and similar tissues into which blood vessels can invade upon angiogenic stimulation are disease states May support angiogenesis. As used herein, the term “angiogenesis-dependent state” is intended to mean a state in which the process of angiogenesis or angiogenesis maintains or increases a pathological state. Angiogenesis is caused by the formation of new blood vessels that arise from hemangioblasts, which are endothelial cell precursors. Both processes result in the formation of new blood vessels and are included within the meaning of the term angiogenesis-dependent state. Similarly, as used herein, the term “angiogenesis” refers to vascularization, such as that caused by angiogenesis, and that caused by branching and sprouting from existing blood vessels, capillaries and venules. It is intended to include new formations.
The term “inhibition of angiogenesis” means effective in reducing the extent, amount or rate of neovascularization. Producing a reduction in the extent, amount or rate of endothelial cell proliferation or migration in tissue is a particular example of inhibiting angiogenesis. Antiangiogenic activity targets the tumor growth process, and in the absence of neovascularization of the tumor tissue, the tumor tissue does not get the necessary nutrients, slows growth, stops further growth, and regresses It is particularly useful in the treatment of any cancer because it eventually necroses and leads to tumor death. Furthermore, the angiogenesis inhibitory activity is particularly effective for the formation of metastases, which also requires primary tumor angiogenesis in order for the metastatic cancer cells to be present in the primary tumor, Establishment at the secondary site is particularly useful for the treatment of any cancer because it requires neovascularization to support metastatic growth.
As used herein, “treatment” and “treating” and the like generally mean obtaining a desired pharmacological and physiological effect. The effect may be prophylactic in terms of preventing or partially preventing the disease, symptom or condition and / or a partial or adverse effect caused by the disease, condition, symptom or disease It may be therapeutic in terms of complete healing. The term “treatment” as used herein encompasses any treatment of a disease in mammals, particularly humans, and (a) is susceptible to the disease but is still diagnosed as having the disease. Preventing the disease from occurring in a subject who has not, (b) inhibiting the disease, ie preventing its onset, or alleviating the disease, ie regressing the disease and / or its symptoms or conditions ,including.
The term “subject” as used herein means a mammal. For example, mammals contemplated by the present invention include livestock animals such as humans, primates, cows, sheep, pigs, horses and the like.
The term “inhibitor” as used in the context of the present invention is a molecule that completely or partially inhibits the activity of NADPH oxidase and / or a molecule that inhibits or reduces the production of reactive oxygen species (ROS). Defined.

Wherein G ₁ is optionally substituted such as H; optionally substituted acyl; optionally substituted acyl C ₁ -C ₆ alkyl; aminocarbonylalkyl (eg, phenylacetamide). alkyl; heterocycloalkylalkyl is optionally substituted; optionally C ₃ -C ₈ cycloalkylalkyl substituted phenylmethyl optionally substituted with (e.g., phenylmethyl or 3-methyl-phenyl-methyl or 4- Optionally substituted arylalkyl, such as optionally substituted phenyl, such as fluorobenzyl or 2-chlorobenzyl or 4-chlorobenzyl or 4-methylbenzyl or 4-bromobenzyl; and pyridine-2 -Optionally substituted such as ylmethyl And are such as pyridine alkyl, optionally selected from heteroarylalkyl substituted; G ₂ is, H; methyl (e.g., methyl) optionally substituted with C ₁ which is optionally substituted, such as ~ C ₆ alkyl; optionally substituted C ₂ -C ₆ alkenyl; optionally substituted C ₂ -C ₆ alkynyl; optionally substituted phenyl (eg, phenyl or 4-fluorophenyl or 3- Chloro-phenyl or 4-methoxyphenyl or 4-nitrophenyl or 2-chlorophenyl or 2-methylphenyl or 4- (trifluoromethyl) phenyl or 4- (trifluoromethoxy) phenyl or 2,5-difluorophenyl or 2, 5-dichlorophenyl or 2-methoxyphenyl or 4- (ben C ₁ optionally substituted -C ₆ alkylaryl; yloxy) phenyl or 3-benzonitrile or 3-phenyl acetamide or 2-chloro-4-like fluorophenyl) aryl which is optionally substituted case Optionally substituted aryl C ₁ -C ₆ alkyl, such as benzyl (eg benzyl) substituted by; optionally substituted benzothiazolyl (eg 1,3-benzothiazolyl-2-yl) or Substituted with pyridinyl (eg, pyridin-2-yl or (4-methylpiperazin-1-yl) sulfonylpyridin-2-yl) or optionally substituted thiazolyl (eg, 4-phenyl-1,3 Optionally substituted, such as -thiazol-2-yl) Optionally substituted alkyl heteroaryl; optionally substituted heteroaryl C ₁ -C ₆ alkyl; optionally substituted C ₂ -C ₆ alkenyl aryl; optionally substituted aryl C ₂ -C ₆ alkenyl; heteroaryl _C 2 -C ₆ alkenyl optionally substituted; optionally _C 2 -C ₆ alkenyl heteroaryl substituted cyclohexyl which is optionally substituted (e.g., cyclohexyl) C ₃ -C ₈ cycloalkyl optionally substituted as; alkyl C ₃ -C ₈ cycloalkyl optionally substituted; when heterocycloalkyl substituted by C ₃ is optionally substituted - C ₈ cycloalkyl _C 1 -C ₆ alkyl; situ _C 1 -C ₆ are selected from alkyl heterocycloalkyl and optionally heterocycloalkyl _C 1 -C ₆ alkyl substituted substituted by; _{G 3 is, - (CH 2) n -R} 1 and - ( CH ₂₎ is selected from _p -R ^{5; R 1 is, -NR 2 R 3; -OR 4} ; morpholinyl optionally substituted (e.g., 4-morpholin-4-yl or 4-benzyl-morpholinylmethyl - 2-yl), optionally substituted pyrrolidinyl (eg, 4-pyrrolidin-1-yl), optionally substituted piperidinyl (eg, 4-phenylpiperidin-1-yl), optionally substituted Dihydroindolyl (eg 2,3-dihydro-1H-indol-1-yl), optionally substituted piperazinyl (eg 3 Optionally substituted hetero, such as methoxyphenylpiperazin-1-yl or 2-chlorophenylpiperazin-1-yl or 3-chlorophenylpiperazin-1-yl or 4-pyridin-2-ylpiperazin-1-yl) Cycloalkyl; optionally substituted heteroaryl; —CHR ⁶ R ⁷ ; optionally substituted acyl and —C (O) NR ² R ³ ; R ² and R ³ are H; Optionally substituted C ₁ -C ₆ alkyl; optionally substituted C ₂ -C ₆ alkenyl; optionally substituted C ₂ -C ₆ alkynyl; optionally substituted phenyl (eg, Optionally substituted aryl, such as phenyl or 2-methoxyphenyl); optionally substituted Is to have C ₁ -C ₆ alkyl aryl; benzyl which is optionally substituted (e.g., benzyl or 3-fluorobenzyl or 2-chlorobenzyl or 3-methoxybenzyl) phenyl C ₁ which is optionally substituted, such as Optionally substituted aryl C ₁ -C ₆ alkyl, such as -C ₆ alkyl; optionally substituted heteroaryl; optionally substituted alkyl heteroaryl; optionally substituted pyridinemethyl ( Optionally substituted heteroaryl C ₁ -C ₆ such as optionally substituted pyridine C ₁ -C ₆ alkyl such as 4-methylpyridin-2-yl or pyridin-3-ylmethyl). Alkyl; optionally substituted C ₂ -C ₆ alkenyl aryl; Optionally substituted aryl C ₂ -C ₆ alkenyl; optionally substituted C ₂ -C ₆ alkenyl heteroaryl; optionally substituted heteroaryl C ₂ -C ₆ alkenyl; optionally substituted C ₃ -C ₈ cycloalkyl; optionally substituted heterocycloalkyl; optionally substituted alkyl C ₃ -C ₈ cycloalkyl; optionally substituted C ₃ -C ₈ cycloalkyl C ₁ -C ₆ alkyl; independently selected from optionally substituted C ₁ -C ₆ alkyl heterocycloalkyl and optionally substituted heterocycloalkyl C ₁ -C ₆ alkyl, or NR ² R ³ is Optionally substituted heteroaryl and optionally substituted morpholini (Eg, morpholin-4-yl or 4-morpholin-1-yl), optionally substituted piperidines (eg, 4-phenylpiperidin-1-yl), optionally substituted dihydroindolyl (eg, 2,3-dihydro-1H-indol-1-yl), optionally substituted piperazinyl (eg 3-methoxyphenylpiperazin-1-yl or 2-chlorophenylpiperazin-1-yl or 3-chlorophenylpiperazine-1 R ⁴ is H; optionally substituted alkoxy C ₁ -C ₆ alkyl; optionally substituted, such as -yl), forming a ring selected from optionally substituted heterocycloalkyl; methyl you are (e.g., methyl) _C 1 -C ₆ alkyl which is optionally substituted, such as; _C 2 -C ₆ alkynyl optionally substituted;; _C 2 _{~C 6} alkenyl substituted by engagement phenyl which is optionally substituted (e.g., phenyl or 4-fluorophenyl or 4-chlorophenyl or 3-chlorophenyl Or 3-methoxyphenyl or 3-dimethylaminophenyl), optionally substituted aryl, such as optionally substituted naphthalenyl (eg, 4-naphthalen-1-yl); optionally substituted C _{1 to} C ₆ alkylaryl; optionally substituted benzyl (eg, benzyl or 2,2,2-trifluoro-1-phenylmethyl or 3-methoxybenzyl or 4-methoxybenzyl or 2-chlorobenzyl or 4- Chlorobenzyl or 3-dimethylaminobenzyl or Such as phenyl methyl), optionally phenylethyl substituted (e.g., 4-chlorophenyl-ethyl), such as, optionally substituted aryl, optionally such as phenyl C ₁ -C ₆ alkyl which is substituted C ₁ -C ₆ alkyl; optionally substituted heteroaryl; optionally substituted alkyl heteroaryl; optionally substituted such as optionally substituted pyridinemethyl (eg, pyridin-3-ylmethyl) Optionally substituted heteroaryl, such as C ₁ -C ₆ alkyl, optionally substituted heteroaryl C ₁ -C ₆ alkyl; optionally substituted C ₂ -C ₆ alkenyl aryl; optionally substituted aryl C ₂ -C ₆ alkenyl; _C 2 is optionally substituted -C ₆ Optionally substituted; heterocycloalkyl optionally substituted; C ₃ -C ₈ cycloalkyl, which is optionally substituted; heteroaryl C ₂ -C ₆ alkenyl optionally substituted; Luque alkenyl heteroaryl Alkyl C ₃ -C ₈ cycloalkyl; optionally substituted C ₃ -C ₈ cycloalkyl C ₁ -C ₆ alkyl; optionally substituted C ₁ -C ₆ alkyl heterocycloalkyl and optionally substituted Selected from heterocycloalkyl C ₁ -C ₆ alkyl; R ⁵ is H; optionally substituted alkoxy; optionally substituted alkoxy C ₁ -C ₆ alkyl; optionally substituted methyl C ₁ -C ₆ alkyl optionally substituted as; optionally substituted _C 1 optionally substituted -C ₆ alkyl aryl; aryl which is optionally substituted; when _C 2 -C ₆ alkynyl which is substituted by; optionally substituted by _C 2 -C ₆ alkenyl which is If aryl heteroaryl substituted by; optionally heteroaryl C ₁ -C ₆ alkyl which is substituted; optionally alkyl substituted heteroaryl is optionally substituted C aryl C ₁ -C ₆ alkyl are _{2 to} C ₆ alkenyl aryl; optionally substituted aryl C _{2 to} C ₆ alkenyl; optionally substituted C _{2 to} C ₆ alkenyl heteroaryl; optionally substituted heteroaryl C _{2 to} C ₆ alkenyl ;
Optionally substituted C ₃ -C ₈ cycloalkyl; optionally substituted heterocycloalkyl; optionally substituted alkyl C ₃ -C ₈ cycloalkyl; optionally substituted C ₃ -C ₈ Cycloalkyl C ₁ -C ₆ alkyl; selected from optionally substituted C ₁ -C ₆ alkyl heterocycloalkyl and optionally substituted heterocycloalkyl C ₁ -C ₆ alkyl; R ⁶ and R ⁷ are , optionally C ₂ -C ₆ alkenyl which is substituted; C ₂ -C ₆ alkynyl optionally substituted; phenyl which is optionally substituted (e.g., 3-methoxyphenyl) optionally substituted, such as It is optionally substituted; optionally C ₁ -C ₆ alkylaryl which is substituted; aryl are And is aryl C ₁ -C ₆ alkyl; optionally substituted; optionally aryl heteroaryl is substituted; optionally heteroaryl C ₁ -C ₆ alkyl optionally substituted; optionally alkyl substituted heteroaryl C ₂ -C ₆ alkenyl aryl; _C 2 -C ₆ alkenyl heteroaryl are optionally substituted; when aryl _C 2 -C ₆ alkenyl substituted by heteroaryl _C 2 is optionally substituted -C ₆ Optionally substituted C ₃ -C ₈ cycloalkyl; optionally substituted heterocycloalkyl; optionally substituted alkyl C ₃ -C ₈ cycloalkyl; optionally substituted C _3- C ₈ cycloalkyl _C 1 -C ₆ alkyl; optionally substituted Or is _C 1 -C ₆ alkyl heterocycloalkyl and optionally are independently selected from heterocycloalkyl _C 1 -C ₆ alkyl which is substituted are, or -CHR ⁶ R ⁷ is optionally substituted Forming an optionally substituted ring selected from heteroaryl, optionally substituted cycloalkyl and optionally substituted heterocycloalkyl; n is an integer selected from 0 to 5; P is an integer selected from 3 to 5; G ₄ is H; optionally substituted acyl; optionally substituted acylamino (eg, 4-fluorophenoxyacetamide); optionally substituted; and are acyl _C 1 -C ₆ alkyl (e.g., N- (pyridin-2-ylmethyl) acetamide or (4-menu Lupiperazin-1-yl) -4-oxobutyl or (4-methylpiperazin-1-yl) -4-oxobutyl or 2-morpholin-4-yl-2-oxoethyl or (4-benzylpiperazin-1-yl) -2 -Oxoethyl or N, N-dimethylacetamide); optionally substituted aminoalkyl (eg 3- (diethylamino) propyl or ethylacetamide or benzylmethylaminomethyl); optionally substituted pentyl (eg isopentyl) or Optionally substituted C ₁ -C ₆ alkyl, such as optionally substituted methyl (eg methyl), or optionally substituted methoxy (eg 2-methoxyethyl or 3-methoxypropyl) , Optionally substituted Etchi (E.g., 3-ethoxypropyl) optionally heteroalkyl is optionally substituted, such, as alkoxy C ₁ -C ₆ alkyl substituted like; C ₂ -C ₆ alkenyl optionally substituted; Optionally substituted C ₂ -C ₆ alkynyl; optionally substituted aryl; optionally substituted C ₁ -C ₆ alkylaryl; optionally substituted phenylmethyl (eg, methyl benzoate or Benzyl, 2-morpholinyl-4-ylbenzyl, 2-morpholinyl-4-ylmethyl-benzyl, (4-methylpiperazin-1-yl) methylbenzyl, 3,5-dimethyloxybenzyl, 3-phenoxybenzyl, or 4-methoxybenzyl Or 2-Met Xylbenzyl or 3-methoxybenzyl or 4-chlorobenzyl or methylphenylacetamidomethyl) or optionally substituted phenylethyl (eg 2-phenylethyl, 4-methoxyphenylethyl or 3-methoxyphenylethyl or 4-hydroxyphenyl) Optionally substituted aryl C ₁ -C ₆ alkyl; optionally substituted heteroaryl; optionally substituted C ₁ -C ₆ alkyl heteroaryl; optionally substituted Optionally substituted thiophenyl C ₁ -C ₆ alkyl such as thiophenylmethyl (eg thiophen-2-ylmethyl or 2-methyl-1,3-thiazol-4-yl) or optionally substituted Is Imidazolylethyl (e.g., imidazol-4-ylethyl) that are indolyl ethyl substituted as imidazolyl C ₁ -C ₆ alkyl optionally substituted, or optionally optionally as (e.g., indol-3-ylethyl ), such as indolyl C ₁ -C ₆ alkyl which is optionally substituted, such as, or furanylmethyl which is optionally substituted (e.g., furan-2-ylmethyl) furanyl C ₁ which is optionally substituted, such as Optionally substituted benzodioxolyl C such as C ₆ alkyl or optionally substituted benzodioxolylmethyl (eg 1,3-benzodioxol-5-ylmethyl) Pirijinirumechi substituted by ₁ -C such as ₆ alkyl, or (Eg, pyridin-3-ylmethyl or pyridin-2-ylmethyl or 6-morpholin-4-ylpyridin-2-yl) methyl), such as optionally substituted pyridinylethyl (eg, 2-pyridin-2-ylethyl) optionally such as pyridinyl _C 1 -C ₆ alkyl substituted, or oxadiazolyl methyl optionally substituted with a (e.g., 3-ethyl-1,2,4-oxadiazol-5-ylmethyl) Optionally substituted pyrazinyl C _1- , such as optionally substituted oxadiazolyl C ₁ -C ₆ alkyl, or optionally substituted pyrazinylmethyl (eg pyrazin-2-ylmethyl) C ₆ such as alkyl, or optionally substituted pyrazol Methyl (e.g., 1-methylpyrazole-3-ylmethyl) such as pyrazolyl _C 1 -C ₆ alkyl which is optionally substituted, such as, when the heteroaryl _C 1 -C ₆ alkyl substituted by; optionally _C 2 -C ₆ alkenyl aryl substituted;
Optionally substituted aryl C ₂ -C ₆ alkenyl; optionally substituted such as optionally substituted phenyl C ₂ -C ₆ alkynyl (eg 3-phenylprop-2-yn-1-yl) and which aryl _C 2 -C ₆ alkynyl; heteroaryl _C 2 -C ₆ alkenyl optionally substituted; when _C 2 -C ₆ alkenyl heteroaryl substituted by _C 3 is optionally substituted -C ₈ cycloalkyl; optionally substituted morpholinyl (eg, 5-morpholin-4-yl) or optionally substituted piperazinyl (eg, 4-methylpiperazinyl) or optionally substituted piperidinyl (eg, Optionally substituted, such as 4-methylbenzyl) piperidin-4-yl) Optionally _C 1 -C ₆ alkyl _C 3 -C ₈ cycloalkyl which is substituted; cyclohexyl _C 1 -C ₆ alkyl which is optionally substituted (e.g., cyclohexylmethyl) If you like by substituted heterocycloalkyl which are C ₃ -C ₈ cycloalkyl C ₁ -C ₆ alkyl; optionally substituted C ₁ -C ₆ alkyl heterocycloalkyl and optionally substituted morpholinylpropyl (eg 3- ( Morpholin-4-yl) propyl or 3-morpholin-4-yl-3-phenylpropyl), optionally substituted morpholinylethyl (eg 2-morpholin-4-ylethyl or 2-morpholin-4-yl) -2-phenylethyl), optionally substituted morpholinylmethyl (E.g., 4-methyl-morpholin-2-yl), such as, if piperazinyl optionally substituted morpholinyl C ₁ -C such as ₆ alkyl, or substituted by pyrazinyl ethyl (e.g. 2- ( Optionally substituted piperazinyl C ₁ -C ₆ alkyl such as or optionally substituted such as 4-acetylpiperazin-1-yl) ethyl or 2- (4-hexanoylpiperazin-1-yl) ethyl) Optionally substituted pyrrolidinyl C ₁ -C ₆ alkyl such as pyrrolidinylpropyl (eg 3- (2-oxopyrrolidin-1-yl) propyl) or optionally substituted Optionally substituted such as tetrahydrofuranylmethyl (eg tetrahydrofuran-2-ylmethyl) Tetrahydropyranyl optionally substituted such as tetrahydrofuranyl C ₁ -C ₆ alkyl or optionally substituted tetrahydropyranylethyl (eg 2-tetrahydro-2H-pyran-2-ylethyl) Piperidine methyl, such as C ₁ -C ₆ alkyl or optionally substituted (eg piperidin-4-ylmethyl, piperidin-3-ylmethyl, 1-methylpiperidin-4-ylmethyl, 1-tert-butyl-1 - carboxylate-4-like pyridinyl C ₁ -C ₆ alkyl which is optionally substituted Irumechi such as Le, optionally selected from heterocycloalkyl C ₁ -C ₆ alkyl which is substituted; G ₅ is, H; situ; _C 1 -C ₆ alkyl which is optionally substituted Optionally substituted; _C 1 -C ₆ alkyl aryl which is optionally substituted; aryl which is optionally substituted; _C 2 -C ₆ alkynyl optionally substituted; _C 2 -C ₆ alkenyl substituted by is aryl _C 1 is -C ₆ alkyl; heteroaryl _C 1 -C ₆ alkyl which is optionally substituted; _C 1 -C ₆ alkyl heteroaryl which is optionally substituted; optionally substituted heteroaryl; Optionally substituted C ₂ -C ₆ alkenyl aryl; optionally substituted aryl C ₂ -C ₆ alkenyl; optionally substituted C ₂ -C ₆ alkenyl heteroaryl; optionally substituted hetero _C 3 -C which are optionally substituted; aryl _C 2 -C ₆ alkenyl _C 3 -C ₈ cycloalkyl _C 1 -C which are optionally substituted; _C 1 -C ₆ alkyl _C 3 -C ₈ cycloalkyl, which is optionally substituted; heterocycloalkyl optionally substituted; cycloalkyl ₆ alkyl; selected from optionally substituted C ₁ -C ₆ alkyl heterocycloalkyl and optionally substituted heterocycloalkyl C ₁ -C ₆ alkyl], and pharmaceuticals thereof Pharmaceutically acceptable salts and pharmaceutically active derivatives are provided.

Preparative HPLC purification was performed on Prep Nova- Pak® HR C1 86 μm, 60 μm, 40 × 30 mm (up to 100 mg) or XTerra® Prep MS C8, 10 μm , 50 × 300 mm (up to 1 g). Perform on HPLC Waters Prep LC 4000 System with column. All purifications are performed with a gradient of MeCN / H ₂ O 0.09% TFA; UV detection 254 nm and 220 nm; flow rate 20 mL / min (up to 50 mg). TLC analysis is performed on Merck Precoated 60 F ₂₅₄ plates. Purification by flash chromatography is carried out on a SiO ₂ support using cyclohexane / EtOAc or DCM / MeOH mixtures as eluent.

Claims (24)

Formula (I):

Wherein G ₁ is H; optionally substituted acyl; optionally substituted acyl C ₁ -C ₆ alkyl; optionally substituted alkyl; optionally substituted C ₃ -C is heteroaryl alkyl which is optionally substituted arylalkyl and optionally substituted by; ₈ cycloalkylalkyl; optionally heterocycloalkylalkyl substituted G ₂ is, H; optionally substituted C ₁ -C ₆ alkyl; optionally substituted C ₂ -C ₆ alkenyl; optionally substituted C ₂ -C ₆ alkynyl; optionally substituted aryl; optionally substituted C _1- C ₆ alkylaryl; location optionally; when aryl _C 1 -C ₆ alkyl substituted by Is substituted optionally; C ₂ -C ₆ alkenyl aryl, which is optionally substituted; a and is heteroaryl is, heteroaryl C ₁ -C ₆ alkyl which is optionally substituted; optionally alkyl substituted heteroaryl heteroaryl _C 2 -C ₆ alkenyl optionally substituted; when _C 2 -C ₆ alkenyl heteroaryl substituted by; _C 3 optionally substituted -C ₈ aryl _C 2 -C ₆ alkenyl which are optionally; C ₃ -C ₈ cycloalkyl _C 1 -C ₆ alkyl which is optionally substituted; alkyl _C 3 -C ₈ cycloalkyl, which is optionally substituted; heterocycloalkyl optionally substituted; cycloalkyl _C 1 -C ₆ alkyl heterocycloalkyl substituted It is selected from optionally heterocycloalkyl _C 1 -C ₆ alkyl which is substituted beauty; _{G 3} is, - _{(CH 2)} n -R ¹ and - _{(CH 2)} is selected from p -R ^{5; R 1} is , —NR ² R ³ ; —OR ⁴ ; optionally substituted heterocycloalkyl; optionally substituted heteroaryl; —CHR ⁶ R ⁷ ; optionally substituted acyl and —C (O) NR is selected from ² R ^{3; R 2} and ^{R 3,} H; _C 2 -C ₆ alkenyl optionally substituted; if _C 1 -C ₆ alkyl substituted by optionally substituted _{C 2} -C ₆ alkynyl; optionally substituted aryl; optionally substituted C ₁ -C ₆ alkylaryl; optionally substituted aryl C ₁ -C ₆ alkynyl Optionally substituted heteroaryl; optionally substituted alkyl heteroaryl; optionally substituted heteroaryl C ₁ -C ₆ alkyl; optionally substituted C ₂ -C ₆ alkenyl aryl; Optionally substituted aryl C ₂ -C ₆ alkenyl; optionally substituted C ₂ -C ₆ alkenyl heteroaryl; optionally substituted heteroaryl C ₂ -C ₆ alkenyl; optionally substituted C ₃ -C ₈ cycloalkyl; optionally substituted heterocycloalkyl; optionally substituted alkyl C ₃ -C ₈ cycloalkyl; optionally substituted C ₃ -C ₈ cycloalkyl C ₁ -C ₆ alkyl; _C 1 -C ₆ Arukiruhete an optionally substituted Are independently selected from heterocycloalkyl C ₁ -C ₆ alkyl or NR ² R ³ is replaced by cycloalkyl and optionally, when the heterocycloalkyl optionally substituted heteroaryl and substituted R ⁴ is H; optionally substituted alkoxy C ₁ -C ₆ alkyl; optionally substituted C ₁ -C ₆ alkyl; optionally substituted C ₂ -C ₆ alkenyl; _C 1 -C ₆ alkylaryl is optionally substituted; aryl which is optionally substituted; when _C 2 -C ₆ alkynyl substituted by aryl _C 1 is optionally substituted - C ₆ alkyl; If heteroaryl is substituted by; optionally substituted Arukiruhe Roariru; is optionally substituted; aryl C ₂ -C ₆ alkenyl optionally substituted; C ₂ -C ₆ alkenyl aryl, which is optionally substituted; optionally heteroaryl C ₁ -C ₆ alkyl which is substituted when heteroaryl _C 2 is substituted by -C ₆ alkenyl;; _C 3 optionally substituted -C ₈ cycloalkyl; If; heterocycloalkyl optionally substituted _C 2 -C ₆ alkenyl heteroaryl which are _C 1 -C ₆ alkyl heterocycloalkyl and optionally substituted; _C 3 -C ₈ cycloalkyl _C 1 -C ₆ alkyl which is optionally substituted; alkyl _C 3 -C ₈ cycloalkyl substituted by If heterocycloalkyl _C 1 -C ₆ a substituted by It is selected from killed; R ⁵ is, H; optionally substituted; C ₁ -C ₆ alkyl which is optionally substituted; alkoxy C ₁ -C ₆ alkyl which is optionally substituted; alkoxy optionally substituted Optionally substituted C ₂ -C ₆ alkenyl; optionally substituted C ₂ -C ₆ alkynyl; optionally substituted aryl; optionally substituted C ₁ -C ₆ alkyl aryl; optionally substituted Aryl C ₁ -C ₆ alkyl; optionally substituted heteroaryl; optionally substituted alkyl heteroaryl; optionally substituted heteroaryl C ₁ -C ₆ alkyl; optionally substituted C ₂ -C ₆ alkenyl aryl; when aryl _C 2 -C ₆ alkenyl substituted by Optionally substituted; C ₃ -C ₈ cycloalkyl, which is optionally substituted; heteroaryl C ₂ -C ₆ alkenyl optionally substituted; C ₂ -C ₆ alkenyl heteroaryl which are optionally substituted _C 1 -C ₆ optionally substituted by; _C 3 -C ₈ cycloalkyl _C 1 -C ₆ alkyl which is optionally substituted; alkyl _C 3 -C ₈ cycloalkyl, which is optionally substituted; heterocycloalkyl Selected from alkylheterocycloalkyl and optionally substituted heterocycloalkyl C ₁ -C ₆ alkyl; R ⁶ and R ⁷ are optionally substituted C ₂ -C ₆ alkenyl; optionally substituted optionally substituted; aryl which is optionally substituted; C ₂ -C ₆ alkynyl Heteroaryl which is optionally substituted; alkyl heteroaryl which is optionally substituted; heteroaryl which is optionally substituted; optionally aryl C ₁ -C ₆ alkyl optionally substituted; C ₁ -C ₆ alkylaryl which are C ₁ -C ₆ alkyl; aryl _C 2 -C ₆ alkenyl optionally substituted; when _C 2 -C ₆ alkenyl optionally substituted aryl _C 2 -C ₆ alkenyl optionally substituted heteroaryl; Optionally substituted heteroaryl C ₂ -C ₆ alkenyl; optionally substituted C ₃ -C ₈ cycloalkyl; optionally substituted heterocycloalkyl; optionally substituted alkyl C ₃ -C ₈ cycloalkyl; _C 3 -C which are optionally substituted Cycloalkyl C ₁ -C ₆ alkyl; optionally are independently selected from heterocycloalkyl C ₁ -C ₆ alkyl optionally substituted with C ₁ -C ₆ alkyl heterocycloalkyl and substituted or -CHR ⁶ R ⁷ is optionally form a ring optionally substituted selected from heterocycloalkyl optionally substituted cycloalkyl and an optionally substituted heteroaryl, substituted; n Is an integer selected from 0 to 5; p is an integer selected from 3 to 5; G ₄ is H; optionally substituted acyl; optionally substituted acylamino; location optionally; _C 1 -C ₆ alkyl which is optionally substituted; acyl _C 1 -C ₆ alkyl substituted by Is substituted optionally; C ₁ -C ₆ alkyl aryl which is optionally substituted; a and are C ₂ -C ₆ alkenyl is; optionally substituted aryl; when C ₂ -C ₆ alkynyl substituted by optionally; heteroaryl _C 1 is optionally substituted -C ₆ alkyl; _C 1 -C ₆ alkyl heteroaryl which is optionally substituted; when heteroaryl substituted by; aryl _C 1 -C ₆ alkyl are heteroaryl C which is optionally substituted; C ₂ -C ₆ alkenyl heteroaryl optionally substituted with; aryl C ₂ -C ₆ alkenyl optionally substituted; C ₂ -C ₆ alkenyl aryl substituted ₂ -C ₆ alkenyl; _C is optionally substituted 3 -C ₈ cycloalk Optionally substituted heterocycloalkyl; optionally substituted C ₁ -C ₆ alkyl C ₃ -C ₈ cycloalkyl; optionally substituted C ₃ -C ₈ cycloalkyl C ₁ -C ₆ Alkyl; selected from optionally substituted C ₁ -C ₆ alkylheterocycloalkyl and optionally substituted heterocycloalkyl C ₁ -C ₆ alkyl; G ₅ is H; optionally substituted C ₁ -C ₆ alkyl; _C 2 -C ₆ alkenyl optionally substituted;
Optionally substituted C ₂ -C ₆ alkynyl; optionally substituted aryl; optionally substituted C ₁ -C ₆ alkylaryl; optionally substituted aryl C ₁ -C ₆ alkyl; C ₂ -C ₆ alkenyl optionally substituted; heteroaryl C ₁ -C ₆ alkyl which is optionally substituted; C ₁ -C ₆ alkyl heteroaryl which is optionally substituted; heteroaryl substituted by Optionally substituted aryl C ₂ -C ₆ alkenyl; optionally substituted C ₂ -C ₆ alkenyl heteroaryl; optionally substituted heteroaryl C ₂ -C ₆ alkenyl; optionally substituted C ₃ -C ₈ cycloalkyl; optionally substituted hete Optionally substituted C ₁ -C ₆ alkyl C ₃ -C ₈ cycloalkyl; optionally substituted C ₃ -C ₈ cycloalkyl C ₁ -C ₆ alkyl; optionally substituted C ₁ -C ₆ alkyl heterocycloalkyl and pyrazolopyridine derivatives represented by] is selected from heterocycloalkyl C ₁ -C ₆ alkyl which is optionally substituted, and pharmaceutically acceptable salts and pharmaceutical Active derivative. The derivative according to claim 1, wherein G ₁ is H. G ₃ is - _{(CH 2)} n -R ^{1, R 1} and n are as defined 請 Motomeko 1 or 2, according to claim 1 or 2 derivative according. G ₃ is - _{(CH 2)} n -R ^{1, R 1} is ^-NR 2 ^{R 3,} are as R 2, ^{R 3} and n are as defined in 請 Motomeko 1 or 2, claim The derivative | guide_body of any one of 1-3. G ₃ is - _{(CH 2)} n -R ^{1, R 1} is ^-NR 2 ^{R 3, R 3} is aryl _C 1 -C ₆ alkyl, ^{R 2} and n are請 Motomeko 1-4 The derivative according to any one of claims 1 to 4, which is as defined in any one of the above. G ₃ is - _{(CH 2)} n -R ^{1, R 1} is heterocycloalkyl, is as n is as defined in any one of 請 Motomeko 1-5, claims 1 to 3 The derivative | guide_body of any one of these. G ₃ is - _{(CH 2)} n -R ^{1, R 1} is heteroaryl, n is as defined in any one of 請 Motomeko 1-6 of claims 1 to 3 The derivative | guide_body of any one. G ₃ is - _{(CH 2)} n -R ^{1, R 1} is ^{-NR 2 R 3, R} 2 is _C 1 -C ₆ alkyl, ^{R 3} and n is請 Motomeko 1-7 it is as defined in any one derivative according to any one of claims 1 to 5. G ₃ is - _{(CH 2)} n -R ^1, n is 1, ^{R 1} is as defined in any one of 請 Motomeko 1-8, any of claims 1 to 8 The derivative according to claim 1. G ₃ is - _{(CH 2)} p -R ^{5, R 5} and p are as defined in any one of 請 Motomeko 1-9, in any one of claims 1-2 Derivatives described. G ₅ is H, derivative according to any one of claims 1 to 10. The following groups:
5-benzyl-2- (2-chlorophenyl) -4- (morpholin-4-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-butyl-2-methyl-5- (pyridin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- [4- (benzyloxy) phenyl] -4-butyl-5- (4-chlorobenzyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- [4- (benzyloxy) phenyl] -4-butyl-5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- [4- (benzyloxy) phenyl] -4-butyl-5- (pyridin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-butyl-2- (2-chloro-4-fluorophenyl) -5- (furan-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-butyl-2- (2-chloro-4-fluorophenyl) -5- (pyridin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-butyl-2- (2-chloro-4-fluorophenyl) -5- (2-methoxyethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-Butyl-2- (2-chloro-4-fluorophenyl) -5- (2-pyridin-2-ylethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H)- Dione;
4-Butyl-2- (2-chloro-4-fluorophenyl) -5- (3,5-dimethoxybenzyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione ;
4-{[Benzyl (methyl) amino] methyl} -2- (2-chloro-4-fluorophenyl) -5- (3-methoxypropyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- [4- (benzyloxy) phenyl] -4-butyl-5- (2-methoxyethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-butyl-2- (2-chloro-4-fluorophenyl) -5- [2- (morpholin-4-ylmethyl) benzyl] -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (3-chlorophenyl) -4- (methoxymethyl) -5- (pyridin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (3-Chlorophenyl) -4- (methoxymethyl) -5- [2- (morpholin-4-ylmethyl) benzyl] -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
2-Benzyl-5- (3-ethoxypropyl) -4-{[(3-fluorobenzyl) (methyl) amino] methyl} -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H ) -Dione;
2- (3-chlorophenyl) -5-methyl-4- (pyrrolidin-1-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
5- (4-Chlorobenzyl) -2- (3-chlorophenyl) -4-{[(3-fluorobenzyl) (methyl) amino] methyl} -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (3-chlorophenyl) -4- (methoxymethyl) -5- (2-pyridin-2-ylethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
5- (4-chlorobenzyl) -4- (methoxymethyl) -2-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2-methyl-4- (3-phenoxypropyl) -5- (pyridin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2-Benzyl-5- (2-methoxyethyl) -4- (pyrrolidin-1-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2-Benzyl-4-{[(3-fluorobenzyl) (methyl) amino] methyl} -5- (2-methoxyethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H ) -Dione;
2- (3-Chlorophenyl) -4-{[(3-fluorobenzyl) (methyl) amino] methyl} -5- (2-pyridin-2-ylethyl) -1H-pyrazolo [4,3-c] pyridine- 3,6 (2H, 5H) -dione;
2- (2-Chloro-4-fluorophenyl) -5- (3,5-dimethoxybenzyl) -4- (methoxymethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H ) -Dione;
2- (2-Chloro-4-fluorophenyl) -5- (2-pyridin-2-ylethyl) -4- (pyrrolidin-1-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (3-Chlorophenyl) -5- (2-pyridin-2-ylethyl) -4- (pyrrolidin-1-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
2- (2-Chloro-4-fluorophenyl) -5- (furan-2-ylmethyl) -4- (methoxymethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
2- (2-Chloro-4-fluorophenyl) -4- (methoxymethyl) -5- (pyridin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
2-Benzyl-5- (3,5-dimethoxybenzyl) -4- (pyrrolidin-1-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (3-Chlorophenyl) -4-{[(3-fluorobenzyl) (methyl) amino] methyl} -5- (2-methoxyethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- [4- (Benzyloxy) phenyl] -5- (pyridin-3-ylmethyl) -4- (pyrrolidin-1-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4- (methoxymethyl) -2-methyl-5- (2-pyridin-2-ylethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (3-chlorophenyl) -5- (2-methoxyethyl) -4- (pyrrolidin-1-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chloro-4-fluorophenyl) -5- (2-methoxyethyl) -4- (pyrrolidin-1-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chloro-4-fluorophenyl) -5- (3-ethoxypropyl) -4- (pyrrolidin-1-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (3-Chlorophenyl) -5- (3-ethoxypropyl) -4-{[(3-fluorobenzyl) (methyl) amino] methyl} -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2-Benzyl-5- (3-ethoxypropyl) -4- (pyrrolidin-1-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- [4- (Benzyloxy) phenyl] -5- (4-chlorobenzyl) -4- (pyrrolidin-1-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H ) -Dione;
2- [4- (Benzyloxy) phenyl] -4-{[(3-fluorobenzyl) (methyl) amino] methyl} -5- (pyridin-3-ylmethyl) -1H-pyrazolo [4,3-c] Pyridine-3,6 (2H, 5H) -dione;
2- [4- (Benzyloxy) phenyl] -5- (4-chlorobenzyl) -4-{[(3-fluorobenzyl) (methyl) amino] methyl} -1H-pyrazolo [4,3-c] pyridine −3,6 (2H, 5H) -dione;
2- [4- (benzyloxy) phenyl] -5-methyl-4- (pyrrolidin-1-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
5- (4-chlorobenzyl) -2-methyl-4- (pyrrolidin-1-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
N- [3-({2- [4- (benzyloxy) phenyl] -3,6-dioxo-4- (pyrrolidin-1-ylmethyl) -1,2,3,6-tetrahydro-5H-pyrazolo [4 , 3-c] pyridin-5-yl} methyl) phenyl] acetamide;
N- {3-[(2- [4- (benzyloxy) phenyl] -4-{[(3-fluorobenzyl) (methyl) amino] methyl} -3,6-dioxo-1,2,3,6 -Tetrahydro-5H-pyrazolo [4,3-c] pyridin-5-yl) methyl] phenyl} acetamide;
2- (3-chlorophenyl) -5- (3-ethoxypropyl) -4- (pyrrolidin-1-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2-methyl-4- (phenoxymethyl) -5- (pyridin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(4-fluorophenoxy) methyl] -2-methyl-5- (pyridin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-[(4-fluorophenoxy) methyl] -5- (2-methoxyethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H)- Dione;
2- (2-chlorophenyl) -4-[(4-fluorophenoxy) methyl] -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2,5-dichlorophenyl) -4-[(4-fluorophenoxy) methyl] -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2,5-dichlorophenyl) -4-[(4-fluorophenoxy) methyl] -5- (2-methoxyethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H ) -Dione;
5- (4-chlorobenzyl) -4-[(4-fluorophenoxy) methyl] -2-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(benzyloxy) methyl] -2-methyl-5- (pyridin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
5- (2-methoxybenzyl) -2-methyl-4- (3-phenoxypropyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(4-Fluorophenoxy) methyl] -2-methyl-5-[(6-morpholin-4-ylpyridin-2-yl) methyl] -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(4-Fluorophenoxy) methyl] -2-methyl-5- [2- (tetrahydro-2H-pyran-2-yl) ethyl] -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(4-Fluorophenoxy) methyl] -2-methyl-5- (2-pyridin-2-ylethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione ;
5- (3-methoxybenzyl) -2-methyl-4- (3-phenoxypropyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2-methyl-4- (3-phenoxypropyl) -5- (2-pyridin-2-ylethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(4-chlorophenoxy) methyl] -5- (3-methoxybenzyl) -2-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(benzyloxy) methyl] -5- (3-ethoxypropyl) -2-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(benzyloxy) methyl] -5- (3-methoxybenzyl) -2-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(4-chlorophenoxy) methyl] -5- (3-ethoxypropyl) -2-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(4-chlorophenoxy) methyl] -2-methyl-5- (pyridin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(benzyloxy) methyl] -2-methyl-5- (2-pyridin-2-ylethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
N- [3-({4-[(benzyloxy) methyl] -2-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo [4,3-c] pyridine-5 -Yl} methyl) phenyl] acetamide;
N- [3-({4-[(4-Chlorophenoxy) methyl] -2-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo [4,3-c] pyridine -5-yl} methyl) phenyl] acetamide;
4-[(4-fluorophenoxy) methyl] -2-methyl-5- (pyridin-3-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-[(4-fluorophenoxy) methyl] -5- (pyridin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
2- (2-Chlorophenyl) -4-[(4-fluorophenoxy) methyl] -5- (pyridin-3-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
4-[(benzyloxy) methyl] -2-methyl-5- (pyridin-3-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-[(4-fluorophenoxy) methyl] -5-[(5-methyl-1,2,4-oxadiazol-3-yl) methyl] -1H-pyrazolo [4 , 3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(benzyloxy) methyl] -2- (2-chlorophenyl) -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4- (4-benzylmorpholin-2-yl) -2- (2-chlorophenyl) -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -5- (3-ethoxypropyl) -4-[(4-fluorophenoxy) methyl] -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H)- Dione;
2- (2-Chlorophenyl) -4-[(4-fluorophenoxy) methyl] -5- (2-pyridin-2-ylethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(4-Chlorophenoxy) methyl] -2- (2-chlorophenyl) -5- (pyridin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
2- (2-Chlorophenyl) -4-[(4-fluorophenoxy) methyl] -5-[(2-methyl-1,3-thiazol-4-yl) methyl] -1H-pyrazolo [4,3-c ] Pyridine-3,6 (2H, 5H) -dione;
4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -5- (2-pyridin-2-ylethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
4-[(benzyloxy) methyl] -2- (2-chlorophenyl) -5- (3-ethoxypropyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
N- [3-({2- (2-chlorophenyl) -4-[(4-fluorophenoxy) methyl] -3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo [4,3 -C] pyridin-5-yl} methyl) phenyl] acetamide;
4-[(4-chlorophenoxy) methyl] -2- (2-chlorophenyl) -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-{[methyl (phenyl) amino] methyl} -5- (2-pyridin-2-ylethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H , 5H) -dione;
2- (2-Chlorophenyl) -5- (3-ethoxypropyl) -4-{[methyl (phenyl) amino] methyl} -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
2- (2-Chlorophenyl) -4-{[methyl (phenyl) amino] methyl} -5- (pyridin-4-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H ) -Dione;
4-[(4-Chlorophenoxy) methyl] -2- (2-chlorophenyl) -5- (pyridin-3-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -5-[(3-ethyl-1,2,4-oxadiazol-5-yl) methyl] -1H-pyrazolo [4,3 -C] pyridine-3,6 (2H, 5H) -dione;
4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -5- (pyridin-4-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione ;
4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -5- (1,3-thiazol-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
tert-Butyl 4-({4-[(benzyloxy) methyl] -2- (2-chlorophenyl) -3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo [4,3-c ] Pyridin-5-yl} methyl) piperidine-1-carboxylate;
4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -5- (piperidin-4-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione ;
4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -5- [3- (diethylamino) propyl] -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H)- Dione;
4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -5- (pyridin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione ;
4-[(benzyloxy) methyl] -2- (2-chlorophenyl) -5- (2-methoxyethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(4-Chlorophenoxy) methyl] -2- (2-chlorophenyl) -5- (pyridin-4-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -5-[(1-methylpiperidin-4-yl) methyl] -1H-pyrazolo [4,3-c] pyridine-3,6 ( 2H, 5H) -dione;
4-[(3-chlorophenoxy) methyl] -2- (2-chlorophenyl) -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -5-methyl-4-[(2,2,2-trifluoro-1-phenylethoxy) methyl] -1H-pyrazolo [4,3-c] pyridine-3,6 (2H , 5H) -dione;
2- (2-chlorophenyl) -5-methyl-4- (3-phenoxypropyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -5- (pyridin-3-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione ;
4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -5-[(5-methyl-1,2,4-oxadiazol-3-yl) methyl] -1H-pyrazolo [4,3 -C] pyridine-3,6 (2H, 5H) -dione;
4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -5-[(2-methyl-1,3-thiazol-4-yl) methyl] -1H-pyrazolo [4,3-c] pyridine −3,6 (2H, 5H) -dione;
4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -5- (pyrazin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione ;
2- (2-Chlorophenyl) -4-{[(3-fluorobenzyl) (methyl) amino] methyl} -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
2- (2-Chlorophenyl) -5-methyl-4-[(4-phenylpiperidin-1-yl) methyl] -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione ;
2- {4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo [4,3-c] pyridine-5 -Yl} -N, N-dimethylacetamide;
2- (2-chlorophenyl) -4-[(3-methoxyphenoxy) methyl] -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-[(4-fluorophenoxy) methyl] -5- (pyridin-4-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
2- (2-chlorophenyl) -4-{[(3-methoxybenzyl) oxy] methyl} -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-chlorophenyl) -5-methyl-4- {3- [methyl (phenyl) amino] propyl} -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-chlorophenyl) -4-{[(4-methoxybenzyl) oxy] methyl} -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-{[(2-chlorobenzyl) oxy] methyl} -2- (2-chlorophenyl) -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4- [3- (2,3-dihydro-1H-indol-1-yl) propyl] -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -5-[(1-methyl-1H-pyrazol-3-yl) methyl] -1H-pyrazolo [4,3-c] pyridine-3 , 6 (2H, 5H) -dione;
2- (2-chlorophenyl) -5-methyl-4-[(naphthalen-1-yloxy) methyl] -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-{[(4-chlorobenzyl) oxy] methyl} -2- (2-chlorophenyl) -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-{[2- (4-chlorophenyl) ethoxy] methyl} -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione ;
4-{[benzyl (methyl) amino] methyl} -2- (2-chlorophenyl) -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -5-[(4-methylmorpholin-2-yl) methyl] -1H-pyrazolo [4,3-c] pyridine-3,6 ( 2H, 5H) -dione;
4-[(Benzyloxy) methyl] -2- (2-chlorophenyl) -5- (piperidin-3-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione ;
2- (2-chlorophenyl) -4-{[3- (dimethylamino) phenoxy] methyl} -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -5-methyl-4-{[methyl (pyridin-2-ylmethyl) amino] methyl} -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H)- Dione;
4-{[(2-chlorobenzyl) oxy] methyl} -2- (2-chlorophenyl) -5- (pyridin-4-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H , 5H) -dione;
4-{[(2-chlorobenzyl) oxy] methyl} -2- (2-chlorophenyl) -5- (pyridin-3-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H , 5H) -dione;
4-{[(2-chlorobenzyl) oxy] methyl} -2- (2-chlorophenyl) -5- (2-methoxyethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -5- (2-methoxyethyl) -4-[(3-methoxyphenoxy) methyl] -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H)- Dione;
2- (2-Chlorophenyl) -4-{[(3-fluorobenzyl) (methyl) amino] methyl} -5- (2-methoxyethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-[(3-methoxyphenoxy) methyl] -5- (pyridin-4-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
4-{[(3-chlorobenzyl) oxy] methyl} -2- (2-chlorophenyl) -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-({[3- (dimethylamino) benzyl] oxy} methyl) -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
2- (2-chlorophenyl) -4-[(diphenylmethoxy) methyl] -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-[(3-methoxyphenoxy) methyl] -5- (pyridin-3-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
2- (2-Chlorophenyl) -4-{[(3-methoxybenzyl) (methyl) amino] methyl} -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
2- (2-Chlorophenyl) -4-{[(3-fluorobenzyl) (methyl) amino] methyl} -5 [(1-methyl-1H-pyrazol-3-yl) methyl] -1H-pyrazolo [4 3-c] pyridine-3,6 (2H, 5H) -dione;
4-{[(2-chlorobenzyl) (methyl) amino] methyl} -2- (2-chlorophenyl) -5- (2-methoxyethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-{[(2-chlorobenzyl) oxy] methyl} -2- (2-chlorophenyl) -5-[(1-methyl-1H-pyrazol-3-yl) methyl] -1H-pyrazolo [4,3- c] Pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -5-methyl-4-{[methyl (pyridin-3-ylmethyl) amino] methyl} -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H)- Dione;
4-{[(2-Chlorobenzyl) (methyl) amino] methyl} -2- (2-chlorophenyl) -5-[(1-methyl-1H-pyrazol-3-yl) methyl] -1H-pyrazolo [4 , 3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-{[(3-methoxybenzyl) (methyl) amino] methyl} -5-[(1-methyl-1H-pyrazol-3-yl) methyl] -1H-pyrazolo [4 , 3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-{[(3-methoxybenzyl) oxy] methyl} -5-[(1-methyl-1H-pyrazol-3-yl) methyl] -1H-pyrazolo [4,3- c] Pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-[(3-methoxyphenoxy) methyl] -5-[(1-methyl-1H-pyrazol-3-yl) methyl] -1H-pyrazolo [4,3-c] pyridine −3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-[(3-methoxyphenoxy) methyl] -5- (pyrazin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -Dione;
2- (2-Chlorophenyl) -5- (2-methoxyethyl) -4-{[(3-methoxyphenyl) (methyl) amino] methyl} -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-{[(3-methoxyphenyl) (methyl) amino] methyl} -5-[(1-methyl-1H-pyrazol-3-yl) methyl] -1H-pyrazolo [4 , 3-c] pyridine-3,6 (2H, 5H) -dione;
4-{[(2-chlorobenzyl) (methyl) amino] methyl} -2- (2-chlorophenyl) -5- (pyridin-3-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3, 6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-{[(3-methoxybenzyl) oxy] methyl} -5- (pyrazin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H , 5H) -dione;
2- (2-Chlorophenyl) -4-{[(3-methoxybenzyl) oxy] methyl} -5- (pyridin-3-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H , 5H) -dione;
2- (2-Chlorophenyl) -4-{[(3-methoxybenzyl) oxy] methyl} -5- (2-methoxyethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-{[(3-fluorobenzyl) (methyl) amino] methyl} -5- (pyridin-3-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3, 6 (2H, 5H) -dione;
4-{[(2-chlorobenzyl) (methyl) amino] methyl} -2- (2-chlorophenyl) -5- (pyrazin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3, 6 (2H, 5H) -dione;
2- (2-chlorophenyl) -4-{[(3-methoxybenzyl) (methyl) amino] methyl} -5- (pyridin-3-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3, 6 (2H, 5H) -dione;
2- (2-chlorophenyl) -4-[(3-methoxyphenoxy) methyl] -5-[(4-methylmorpholin-2-yl) methyl] -1H-pyrazolo [4,3-c] pyridine-3, 6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-{[4- (3-methoxyphenyl) piperazin-1-yl] methyl} -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H , 5H) -dione;
2- (2-Chlorophenyl) -4-{[(3-methoxyphenyl) (methyl) amino] methyl} -5- (pyridin-3-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3, 6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-{[4- (2-chlorophenyl) piperazin-1-yl] methyl} -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-{[4- (3-chlorophenyl) piperazin-1-yl] methyl} -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-{[(2-chlorobenzyl) oxy] methyl} -2- (2-methoxyphenyl) -5- (pyridin-3-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 ( 2H, 5H) -dione;
4-{[(2-chlorobenzyl) oxy] methyl} -2- (2-chlorophenyl) -5- (pyrazin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H , 5H) -dione;
2- (2-Chlorophenyl) -4-{[methyl (pyridin-2-ylmethyl) amino] methyl} -5- (pyridin-3-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -5-[(1-methyl-1H-pyrazol-3-yl) methyl] -4-{[methyl (pyridin-2-ylmethyl) amino] methyl} -1H-pyrazolo [4 3-c] pyridine-3,6 (2H, 5H) -dione;
4-{[(3-methoxybenzyl) oxy] methyl} -2- (2-methoxyphenyl) -5- (pyrazin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 ( 2H, 5H) -dione;
4-{[(3-methoxybenzyl) oxy] methyl} -2- (2-methoxyphenyl) -5-[(1-methyl-1H-pyrazol-3-yl) methyl] -1H-pyrazolo [4,3 -C] pyridine-3,6 (2H, 5H) -dione;
2- (2-chlorophenyl) -4-{[(3-methoxybenzyl) (methyl) amino] methyl} -5- (pyrazin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3, 6 (2H, 5H) -dione;
4-[(benzyloxy) methyl] -2- (2-methoxyphenyl) -5-[(1-methyl-1H-pyrazol-3-yl) methyl] -1H-pyrazolo [4,3-c] pyridine- 3,6 (2H, 5H) -dione;
4-[(3-methoxyphenoxy) methyl] -2- (2-methoxyphenyl) -5-[(1-methyl-1H-pyrazol-3-yl) methyl] -1H-pyrazolo [4,3-c] Pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -5-[(1-methyl-1H-pyrazol-3-yl) methyl] -4-{[methyl (pyridin-3-ylmethyl) amino] methyl} -1H-pyrazolo [4 3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-Chlorophenyl) -4-{[methyl (pyridin-2-ylmethyl) amino] methyl} -5- (pyrazin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
2- (2-methoxyphenyl) -4-{[4- (3-methoxyphenyl) piperazin-1-yl] methyl} -5-methyl-1H-pyrazolo [4,3-c] pyridine-3,6 ( 2H, 5H) -dione;
2- (2-methoxyphenyl) -5-methyl-4-[(4-pyridin-2-ylpiperazin-1-yl) methyl] -1H-pyrazolo [4,3-c] pyridine-3,6 (2H , 5H) -dione;
2- (2-Chlorophenyl) -5-methyl-4-[(4-pyridin-2-ylpiperazin-1-yl) methyl] -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H) -dione;
4-{[(2-chlorobenzyl) oxy] methyl} -2- (2-methoxyphenyl) -5- (pyrazin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 ( 2H, 5H) -dione;
4-[(Benzyloxy) methyl] -2- (2-methoxyphenyl) -5- (pyrazin-2-ylmethyl) -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H)- Dione;
2- (2-Chlorophenyl) -5-[(1-methyl-1H-pyrazol-3-yl) methyl] -4-[(pyridin-3-ylmethoxy) methyl] -1H-pyrazolo [4,3-c] Pyridine-3,6 (2H, 5H) -dione; and
2- (2-Chlorophenyl) -5- (pyrazin-2-ylmethyl) -4-[(pyridin-3-ylmethoxy) methyl] -1H-pyrazolo [4,3-c] pyridine-3,6 (2H, 5H ) -Dione
The derivative according to any one of claims 1 to 11, which is selected from:   A pharmaceutical composition comprising at least one derivative according to any one of claims 1 to 12 and a pharmaceutically acceptable carrier, diluent or excipient thereof.   The derivative according to any one of claims 1 to 12, which is used as a medicine. Cardiovascular disorders, respiratory disorders, metabolic disorders, skin disorders, bone disorders, neuroinflammatory and / or neurodegenerative disorders, renal diseases, reproductive disorders, diseases affecting the eye and / or lens, and / or effects on the inner ear Condition, inflammatory disorder, liver disease, pain, cancer, allergic disorder, traumatic systemic disorder, septic, hemorrhagic and anaphylactic shock, gastrointestinal disease or disorder, angiogenesis, angiogenesis dependent condition, and nicotine 13. Pils according to any one of claims 1 to 12, for use in the treatment of a disease or condition selected from other diseases and / or disorders associated with amidoadenine dinucleotide phosphate oxidase (NADPH oxidase). A pharmaceutical composition comprising a zolopyridine derivative. Formula (VIII):

Wherein, ^{R 8} is methyl, _C 1 -C ₆ alkyl such as ethyl, propyl, isopropyl or _{butyl, G 2, G 3, G} 4 and _{G 5} are both a 請 Motomeko 1-14 Or as defined in item 1)
Intermediate shown by Formula (X):

Wherein, ^{R 8} is methyl, _C 1 -C ₆ alkyl such as ethyl, propyl, isopropyl or _butyl, G 2, _{G 3} and _{G 5} are any one of 請 Motomeko 1-14 As defined in
Intermediate shown by Formula (XII):

Wherein, ^{R 8} is methyl, ethyl, propyl, _C 1 -C ₆ alkyl such as isopropyl or butyl, _{G 2} and _{G 5} are as defined in any one of 請 Motomeko 1-14 (That's right)
Intermediate shown by Formula (XIII):

Wherein, ^{R 8} is methyl, _C 1 -C ₆ alkyl such as ethyl, propyl, isopropyl or _butyl, G 2, _{G 4} and _{G 5} are any one of 請 Motomeko 1-14 As defined in
Intermediate shown by A process for the preparation of an intermediate of formula (VII) with an amine of formula (II) comprising:

Wherein, ^{R 8} and ^{R 9,} methyl, ethyl, propyl, _C 1 -C ₆ alkyl such as isopropyl or _butyl, is _{G 2, G 3, G 4} , G 5, 請 Motomeko 1-14 A method as defined in any one of the above. A method for preparing an intermediate of formula (X) comprising reacting a compound of formula (IV) with an acyl chloride of formula (IX),

Wherein, ^{R 8} is methyl, ethyl, propyl, _C 1 -C ₆ alkyl such as isopropyl or _{butyl, G 2, G 3, G} 5 is in any one of 請 Motomeko 1-14 A method that is as defined. A process for preparing an intermediate of formula (XII) comprising reacting a compound of formula (IV) with a trialkylorthoester of formula (IX),

Wherein, ^{R 8} and ^{R 9,} methyl, ethyl, propyl, _C 1 -C ₆ alkyl such as isopropyl or butyl, _{G 2} and _{G 5} is, in any one of 請 Motomeko 1-14 A method that is as defined. A process for preparing an intermediate of formula (XIII) comprising reacting a compound of formula (XII) with an amine of formula (II),

Wherein, ^{R 8} is methyl, ethyl, propyl, _C 1 -C ₆ alkyl such as isopropyl or _butyl, G 2, _{G 4} and _{G 5} are, in any one of 請 Motomeko 1-14 A method that is as defined. A process for the preparation of a compound of formula (I) comprising the step of cyclizing a compound of formula (VIII) in the presence of a base,

Wherein, ^{R 8} is a _C 1 -C ₆ alkyl such as methyl, ethyl, propyl, isopropyl or butyl, ^{G 1} is _{H, G 2, G 3,} G 4 and _{G 5} are billed Item 15. A method as defined in any one of Items 1-14 .